Pathways to Impact: Insights from Research Partnerships in Uganda and India

This article sets out a perspective from the United Kingdom’s Department for International Development (DFID) on the challenges of achieving research uptake. Two country case studies are presented from India and Uganda, which explore research projects under the Economic and Social Research Council ESRC-DFID-funded Raising Learning Outcomes programme. These case studies focus on relationships between the key stakeholders that enable policy debate relevant to the funded research. They are not a direct assessment of the impact that this research has had. Rather, this article explores the messy and iterative processes that DFID advisers are engaged in within the networks that they are embedded (and those that they are not), the way that they use partnerships to access evidence and promote it into policy debate, and the other drivers that matter. This article is important as a contribution to ongoing efforts to improve the quality and usage of education evidence in low-income contexts.Department for International Development (DFID)Economic and Social Research Council (ESRC

Stories of Student Success in Title I Elementary Schools

The purpose of this study was to examine factors present in schools with students who performed higher or demonstrated greater improvement on SOL(Standards of Learning) tests that might have been expected based on student demographics. The study identified factors present in these schools that contributed to their success. The study examined four Title I elementary schools, including three designated as high achieving and one as low achieving for purposes of comparison. The study was initially designed to examine equal numbers of schools representing each phenomenon (high and low achieving); however, the perceived pressure associated with state and local reform efforts narrowed the pool of potential study participants. An in-depth examination in each school included interviews with principals, teachers, and parents; observations; and document reviews. Qualitative methods of analysis were employed

The Global Care Ecosystems of 3D Printed Assistive Devices

The popularity of 3D printed assistive technology has led to the emergence of new ecosystems of care, where multiple stakeholders (makers, clinicians, and recipients with disabilities) work toward creating new upper limb prosthetic devices. However, despite the increasing growth, we currently know little about the differences between these care ecosystems. Medical regulations and the prevailing culture have greatly impacted how ecosystems are structured and stakeholders work together, including whether clinicians and makers collaborate. To better understand these care ecosystems, we interviewed a range of stakeholders from multiple countries, including Brazil, Chile, Costa Rica, France, India, Mexico, and the U.S. Our broad analysis allowed us to uncover different working examples of how multiple stakeholders collaborate within these care ecosystems and the main challenges they face. Through our study, we were able to uncover that the ecosystems with multi-stakeholder collaborations exist (something prior work had not seen), and these ecosystems showed increased success and impact. We also identified some of the key follow-up practices to reduce device abandonment. Of particular importance are to have ecosystems put in place follow up practices that integrate formal agreements and compensations for participation (which do not need to be just monetary). We identified that these features helped to ensure multi-stakeholder involvement and ecosystem sustainability. We finished the paper with socio-technical recommendations to create vibrant care ecosystems that include multiple stakeholders in the production of 3D printed assistive devices

Organic thermal maturity as a proxy for frictional fault heating: Experimental constraints on methylphenanthrene kinetics at earthquake timescales

Biomarker thermal maturity is widely used to study burial heating of sediments over millions of years. Heating over short timescales such as during earthquakes should also result in measurable increases in biomarker thermal maturity. However, the sensitivity of biomarker thermal maturity reactions to short, higher-temperature heating has not been established. We report on hydrous pyrolysis experiments that determine the kinetic parameters of methylphenanthrene maturation at timescales and temperatures relevant to earthquake heating. Samples of Woodford Shale were heated at temperatures up to 343 °C over 15–150 min. The thermal maturity of the samples as measured by the methylphenanthrene index-1 (MPI-1) increased with heating time and temperature. We find that MPI-1 increases with time and temperature consistent with a first-order kinetic model and Arrhenius temperature relationship. Over the timescales tested here, MPI-1 is strongly affected by maximum temperature and less sensitive to heating duration. Production of new phenanthrene isomers and expulsion of a liquid pyrolyzate also occurred. Differential expulsion of methylphenanthrene isomers affected the apparent maturity of the rock at lower temperatures and may need to be considered for organic-rich fault rocks. Our results demonstrate that the overall MPI-1 reaction extent in both the rock and pyrolyzate are a useful measure of thermal maturity and reflect temperature history during rapid heating

Aquaporins influence seed dormancy and germination in response to stress

Aquaporins influence water flow in plants, yet little is known of their involvement in the water‐driven process of seed germination. We therefore investigated their role in seeds in the laboratory and under field and global warming conditions. We mapped the expression of tonoplast intrinsic proteins (TIPs) during dormancy cycling and during germination under normal and water stress conditions. We found that the two key tonoplast aquaporins, TIP3;1 and TIP3;2, which have previously been implicated in water or solute transport, respectively, act antagonistically to modulate the response to abscisic acid, with TIP3;1 being a positive and TIP3;2 a negative regulator. A third isoform, TIP4;1, which is normally expressed upon completion of germination, was found to play an earlier role during water stress. Seed TIPs also contribute to the regulation of depth of primary dormancy and differences in the induction of secondary dormancy during dormancy cycling. Protein and gene expression during annual cycling under field conditions and a global warming scenario further illustrate this role. We propose that the different responses of the seed TIP contribute to mechanisms that influence dormancy status and the timing of germination under variable soil conditions

End-to-End Document Classification and Key Information Extraction using Assignment Optimization

We propose end-to-end document classification and key information extraction (KIE) for automating document processing in forms. Through accurate document classification we harness known information from templates to enhance KIE from forms. We use text and layout encoding with a cosine similarity measure to classify visually-similar documents. We then demonstrate a novel application of mixed integer programming by using assignment optimization to extract key information from documents. Our approach is validated on an in-house dataset of noisy scanned forms. The best performing document classification approach achieved 0.97 f1 score. A mean f1 score of 0.94 for the KIE task suggests there is significant potential in applying optimization techniques. Abation results show that the method relies on document preprocessing techniques to mitigate Type II errors and achieve optimal performance.Comment: 10 pages, 5 figure

Transgenic mice expressing LHX3 transcription factor isoforms in the pituitary: Effects on the gonadotrope axis and sex-specific reproductive disease

The LHX3 transcription factor plays critical roles in pituitary and nervous system development. Mutations in the human LHX3 gene cause severe hormone deficiency diseases. The gene produces two mRNAs which can be translated to three protein isoforms. The LHX3a protein contains a central region with LIM domains and a homeodomain, and a carboxyl terminus with the major transactivation domain. LHX3b is identical to LHX3a except that it has a different amino terminus. M2-LHX3 lacks the amino terminus and LIM domains of LHX3a/b. In vitro experiments have demonstrated these three proteins have different biochemical and gene regulatory properties. Here, to investigate the effects of overexpression of LHX3 in vivo, the alpha glycoprotein subunit ( ΑGSU ) promoter was used to produce LHX3a, LHX3b, and M2-LHX3 in the pituitary glands of transgenic mice. Alpha GSU-beta galactosidase animals were generated as controls. Male ΑGSU-LHX3a and ΑGSU-LHX3b mice are infertile and die at a young age as a result of complications associated with obstructive uropathy including uremia. These animals have a reduced number of pituitary gonadotrope cells, low circulating gonadotropins, and possible sex hormone imbalance. Female ΑGSU-LHX3a and ΑGSU-LHX3b transgenic mice are viable but have reduced fertility. By contrast, ΑGSU-M2-LHX3 mice and control mice expressing beta galactosidase are reproductively unaffected. These overexpression studies provide insights into the properties of LHX3 during pituitary development and highlight the importance of this factor in reproductive physiology. J. Cell. Physiol. 212: 105–117, 2007. © 2007 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/56051/1/21010_ftp.pd

Biomarkers heat up during earthquakes: New evidence of seismic slip in the rock record

During earthquakes, faults heat up due to frictional work. However, evidence of heating from paleoearthquakes along exhumed faults remains scarce. Here we describe a method using thermal maturation of organic molecules in sedimentary rock to determine whether a fault has experienced differential heating compared to surrounding rocks. We demonstrate the utility of this method on an ancient, pseudotachylyte-hosting megathrust at Pasagshak Point, Alaska. Measurements of the ratio of thermally stable to thermally unstable compounds (diamondoids/n-alkanes) show that the melt-bearing rocks have higher thermal maturity than surrounding rocks. Furthermore, the mineralogy of the survivor grains and the presence of any organic molecules allow us to constrain the temperature rise during the ancient earthquakes to 840–1170 °C above ambient temperatures of ∼260 °C. From this temperature rise, we estimate that the frictional work of the earthquake was ∼105–228 MJ/m2. Using experimental friction measurements as a constraint, we estimate that the minimum slip necessary for heating was ∼1–8 m. This paper demonstrates that biomarkers will be a useful tool to identify seismic slip along faults without frictional melt

A randomised study of rituximab and belimumab sequential therapy in PR3 ANCA-associated vasculitis (COMBIVAS): design of the study protocol

Background: Sequential B cell-targeted immunotherapy with BAFF antagonism (belimumab) and B cell depletion (rituximab) may enhance B cell targeting in ANCA-associated vasculitis (AAV) through several mechanisms. Methods: Study design: COMBIVAS is a randomised, double-blind, placebo-controlled trial designed to assess the mechanistic effects of sequential therapy of belimumab and rituximab in patients with active PR3 AAV. The recruitment target is 30 patients who meet the criteria for inclusion in the per-protocol analysis. Thirty-six participants have been randomised to one of the two treatment groups in a 1:1 ratio: either rituximab plus belimumab or rituximab plus placebo (both groups with the same tapering corticosteroid regimen), and recruitment is now closed (final patient enrolled April 2021). For each patient, the trial will last for 2 years comprising a 12-month treatment period followed by a 12-month follow-up period. Participants: Participants have been recruited from five of seven UK trial sites. Eligibility criteria were age ≥ 18 years and a diagnosis of AAV with active disease (newly diagnosed or relapsing disease), along with a concurrent positive test for PR3 ANCA by ELISA. Interventions: Rituximab 1000 mg was administered by intravenous infusions on day 8 and day 22. Weekly subcutaneous injections of 200 mg belimumab or placebo were initiated a week before rituximab on day 1 and then weekly through to week 51. All participants received a relatively low prednisolone (20 mg/day) starting dose from day 1 followed by a protocol-specified corticosteroid taper aiming for complete cessation by 3 months. Outcomes: The primary endpoint of this study is time to PR3 ANCA negativity. Key secondary outcomes include change from baseline in naïve, transitional, memory, plasmablast B cell subsets (by flow cytometry) in the blood at months 3, 12, 18 and 24; time to clinical remission; time to relapse; and incidence of serious adverse events. Exploratory biomarker assessments include assessment of B cell receptor clonality, B cell and T cell functional assays, whole blood transcriptomic analysis and urinary lymphocyte and proteomic analysis. Inguinal lymph node and nasal mucosal biopsies have been performed on a subgroup of patients at baseline and month 3. Discussion: This experimental medicine study provides a unique opportunity to gain detailed insights into the immunological mechanisms of belimumab-rituximab sequential therapy across multiple body compartments in the setting of AAV. Trial registration: ClinicalTrials.gov NCT03967925. Registered on May 30, 2019